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Growth Hormone Axis

AOD-9604

Growth hormone fragment designed to keep GH's fat-burning signal without its effects on blood sugar or IGF-1; human results were modest.

RestrictedEvidence level 3 of 5: Limited human dataAlso: Anti-Obesity Drug 9604, HGH Fragment 176-191 (Tyr-modified), Tyr-hGH(177-191)

Overview

AOD-9604 is a small fragment taken from the tail end of the growth hormone molecule, with one added amino acid for stability. It was designed to keep growth hormone's ability to break down fat while avoiding its effects on blood sugar, IGF-1 and tissue growth. Early animal studies were encouraging, and human trials confirmed it is well tolerated. But a 2007 phase 2b obesity trial did not produce meaningful weight loss, and the drug program was stopped. Today it is used off-label as a gentle adjunct for fat loss and, in animal studies, for cartilage support. Any effect is slow and subtle; it does not replace nutrition, training or proven weight-loss medicines.

Classification
Synthetic 16-amino-acid peptide analog of the human growth hormone C-terminus (residues 176–191 plus N-terminal tyrosine)
Route
Subcutaneous
Half-life
~30 minutes (SC)

Mechanism of action

Primary targetAdipocyte lipolytic pathways (independent of the GH receptor)
  1. Reaches fat tissueActs on adipocytes without meaningfully activating the GH receptor.
  2. Stimulates lipolysisIncreases hormone-sensitive lipase activity and triglyceride breakdown.
  3. Inhibits lipogenesisReduces new fat synthesis within fat cells.
  4. Spares glucose and IGF-1No rise in IGF-1 or insulin resistance seen in trials.
  5. Chondrocyte signalingAnimal data suggest cartilage-protective effects in osteoarthritis.
Downstream effects
  • Fat mobilization (modest)
  • Neutral glucose and IGF-1
  • Cartilage support (animal)

Researched for

  • Obesity (phase 2b, unsuccessful)
  • Osteoarthritis and cartilage repair (animal)
  • Fat loss adjunct
  • Food ingredient safety (GRAS)

Research notes

  • Animal studies (Ng 2000; Heffernan 2001) showed fat reduction without diabetogenic effects of full-length GH.
  • Phase 2b obesity trial (2007, ~500 subjects) failed to show clinically meaningful weight loss vs placebo; development was stopped.
  • Pooled safety data (Stier 2013) found tolerability similar to placebo, with no change in IGF-1 or glucose tolerance.
  • Joint benefits are supported only by animal osteoarthritis models.

Reported side effects

  • Injection-site redness or mild pain
  • Headache (occasional)
  • Generally well tolerated in trials

Contraindications & cautions

  • Active malignancy
  • Pregnancy or breastfeeding
  • Severe hepatic or renal impairment
  • Known hypersensitivity to GH fragments

Lab monitoring

  • Fasting glucose and HbA1c
  • Lipid panel
  • IGF-1 (baseline)
  • Thyroid panel
  • Weight, waist and body composition

Dosing and pricing for AOD-9604

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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